Our study aimed to develop an “ex tempore” reconstitutable, viscosity enhancer- and preservative-free meloxicam (MEL)-loaded polymeric micelle formulation, via Quality by Design (QbD) approach, exploiting the nose-to-brain pathway, as a suitable tool in the treatment of neuroinflammation. The anti-neuroinflammatory effect of nose-to-brain NSAID polymeric micelles was not studied previously, therefore its investigation is promising. Critical product parameters, encapsulation efficiency (89.4%), Z-average (101.22 ± 2.8 nm) and polydispersity index (0.149 ± 0.7) and zeta potential (−25.2 ± 0.4 mV) met the requirements of the intranasal drug delivery system (nanoDDS) and the targeted profile liquid formulation was transformed into a solid preservative-free product by freeze-drying. The viscosity (32.5 ± 0.28 mPas) and hypotonic osmolality (240 mOsmol/L) of the reconstituted formulation provides proper and enhanced absorption and probably guarantees the administration of the liquid dosage form (nasal drop and spray). The developed formulation resulted in more than 20 times faster MEL dissolution rate and five-fold higher nasal permeability compared to starting MEL. The prediction of IVIVC confirmed the great potential for in vivo brain distribution of MEL. The nose-to-brain delivery of NSAIDs such as MEL by means of nanoDDS as polymeric micelles offers an innovative opportunity to treat neuroinflammation more effectively.

中文翻译：

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基于设计的基于质量的配制用于鼻内给药的美洛昔康聚合物胶束的配方研究。

我们的研究旨在通过“质量设计”（QbD）方法，开发一种“临时”，可重构，不含增粘剂和防腐剂的美洛昔康（MEL）聚合物胶束制剂，它是通过鼻-脑途径开发的。治疗神经炎症的工具。鼻-脑NSAID聚合物胶束的抗神经炎作用尚未进行过研究，因此其研究前景广阔。关键的产品参数，包封效率（89.4％），Z均值（101.22±2.8 nm）和多分散指数（0.149±0.7）和zeta电位（−25.2±0.4 mV）满足鼻内给药系统（nanoDDS）的要求通过冷冻干燥将目标轮廓的液体制剂转化为无固体的固体产品。粘度（32.5±0。重新配制的制剂的浓度为28 mPas）和低渗渗透压（240 mOsmol / L）可提供适当的吸收并增强吸收，并可能保证液体剂型（滴鼻剂和喷雾剂）的给药。与开始的MEL相比，开发的配方可提高MEL的溶解速度20倍以上，并提高鼻通透性5倍。IVIVC的预测证实了MEL在体内脑内分布的巨大潜力。NSAID（例如MEL）通过纳米DDS作为高分子胶束从鼻到脑的传递提供了一个创新的机会，可以更有效地治疗神经炎症。与开始的MEL相比，开发的配方可提高MEL的溶解速度20倍以上，并提高鼻通透性5倍。IVIVC的预测证实了MEL在体内脑内分布的巨大潜力。NSAID（例如MEL）通过纳米DDS作为高分子胶束从鼻到脑的传递提供了一个创新的机会，可以更有效地治疗神经炎症。与开始的MEL相比，开发的配方可提高MEL的溶解速度20倍以上，并提高鼻通透性5倍。IVIVC的预测证实了MEL在体内脑内分布的巨大潜力。NSAID（例如MEL）通过纳米DDS作为高分子胶束从鼻到脑的传递提供了一个创新的机会，可以更有效地治疗神经炎症。